Antennipaedia

Summary : how to build an animal

1. Establish axes (front-back, top-bottom,
left-right) by concentrations of
proteins, or by unequal cell division

2. More precise segment identification

(this is the head, this is the pelvis, etc)
Bithorax, Abdomen A & B, Hox genes

3. Switch on the appropriate structures

for that part: eyes, limbs, kidneys, etc.
Pax, Pitx1, tinman, etc genes
 Homeotic Genes (Hox)
A family of genes involved in development, that
share high homology in a particular domain
Transcrption factors
Shared region is the DNA binding domain
 What are toolkit genes?
-- determine what is built, and where
-- encode signals (ligands), receptors, or transcription factors

Ligand binds to receptor

Receptor activates TF

TF

TF switches on protein
DNA production

Involved in switching on genes that will either construct the organs or release
signals that tell the cells what to do (how long to divide, what types of tissue to
make & when)
Hox genes trace back to the common
ancestor of animals

Changes in the regulatory pathways of these genes likely spurred or permitted

diversity of body plans.
Pax-6 Ectopic (out of place) expression of
fly eyeless (Pax-6) induces the
formation of ectopic eyes in fruit flies.
A) Cuticle of an adult head in
which both antennae formed eye
structures.

B) Dissected Wing with a

large outgrowth of eye tissue.

D) Dissected middle leg with an

eye outgrowth on the base of the
tibia.
All of these are due to Fly Pax-6
Pax-6 : a shared eye control gene

Fruit fly
Human
Mouse

Aniridia lack of an
iris, caused by
mutation in Pax6
Development of limbs
Head

Limb
buds

Fgf, Shh, Hox are

toolkit genes

Shh = Sonic HedgeHog

Heterocrhony
 (a) Early in
development

FISH LIMB BUD MOUSE LIMB BUD

(b) Later in
development

Head Tail Head Tail

(c) Hypothesis
Foot

Fin Hoxd-11 expression as in fish,

Hoxd-11 expression
along long axis of limb followed by expression toward head
 Four Eons
200,000 years ago.
Homo sapiens

Macro-fossils

Eukaryotic cells,
still single cell
organisms

Life, single cells,

prokaryotic cells

19
EG Nisbet & NH Sleep, 2001. The habitat and nature of early life. Nature 409:1083-1091
Genome Size and Complexity
Gene Duplications and the
Origin of New Genes
 What is a gene family?
A gene family is a set of several similar genes, formed by
duplication of a single original gene.
Gene duplication and may be the most important way of
generating new genes in eukaryotes.
The original gene is still functional. The duplicated copy can
acquire useful mutations and become a new gene. Or
differential regulation can start the expression of the gene in
a different cell type or in different environmental conditions
Both in prokaryotes and eukaryotes biologists routinely find
clusters of similar genes.
 Gene Families
Genes are categorized into families based on shared
nucleotide or protein sequences.
Generally members of a gene family share somewhat similar
biochemical functions
Duplications and the Evolution of Gene Families
Misalignment during meiosis and unequal crossing-over
 Example: How has trichromatic vision been
achieved in the Primates?
Part of TEX 28 was also duplicated

New copies are tuned to different wavelengths by selection on the 3 amino acids
The evolution of trichromatic color vision by opsin gene duplication in New World and Old World primates
DULAI KS, VON DORNUM M, MOLLON JD, et al.
GENOME RESEARCH 9 (7): 629-638 JUL 1999
Some copies may loose any known function and become pseudo genes.
Immunoglobulin Superfamily
The most numerous family in the human
genome, 765 members identified
A large group of cell surface and soluble
proteins that are involved in the recognition,
binding, or adhesion processes of cell. Many
involved in the immune response.
Members can be found in simple organisms
(Sponges)
Also found in bacteria. (Horizontal gene
transfer from prokaryotes to eukaryotes?)
Immunoglobulin Superfamiliy
 Transposable Elements
Sequences of DNA that can make copies
of themselves and insert them in other
parts of the genome
First discovered by Barbara McClintock in
the 50s
Types of Transposable Elements
DNA transposons. Use the enzyme transposase.
Range in size from a few hundred to several
thousands base pairs.
Retrotransposons
LTR retrotransposons. Endogenous retroviruses.
LINES (Long Intrerspersed Elements). (1,000 to 7,000 bp).
SINES (Short Intrerspersed Elements).(100 to 400 bases)
One particular class of SINEs, the Alu sequences (300 bp)
are unique to primates

Vast majority is non-functional in humans

Types of Transposons
Retroviral Genome and
Replication Cycle
Structure of Retrotransposons

Lines

Sines
How did They Spread?

Example, placenta
HERV and Placenta Development
 EXAMPLE: How retrotransposons Copy and Jump

HOW TRANSPOSABLE ELEMENTS SPREAD

DNA 1. A long interspersed

element (LINE) exists
Cytoplasm Original location of LINE in DNA.
Line mRNA
RNA polymerase
2. RNA polymerase
LINE transcribes LINE.
protein
Two LINE proteins 3. LINE mRNA exits
LINE mRNA nucleus and is
translated.
Ribosome 4. LINE proteins and
mRNA enter nucleus.
cDNA
Reverse
transcriptase 5. One protein, integrase
nicks DNA. The other
mRNA protein, reverse
transcriptase, makes LINE
cDNA from RNA. DNA
polymerase makes
cDNA double stranded.
Original copy New copy
6. New copy of LINE
is integrated into genome.
 Endogenous Retroviruses
Retroviral sequences permanently residing in our
genome. These sequences contain inactive
sequences once acting as promoters, and genes for
RT and integrase.
First discovered in birds Avian Leukosis Virus
In particular conditions they can reactivate
Phoenix reactivated in the lab

Contain regulatory sequences and may have altered

the expression of genes adjacent to the integration
site
Important for evolution of new features. Example,
placenta.
Mutations: new alleles or new genes?

New allele: same location (locus), small

change. Does not increase the amount of
information in the genome
limited amount of change in function
New gene: increases information, at least
part is in a new location -- may be near by or
more distant
may involve large change in function, especially
as more change accumulates over time
May involve the evolution of a new gene or a new
domain
Before we discuss the evolution of new domains we will
discuss one mechanism of transposition
 Transposable Elements and the
Evolution of New Exons
Transposable elements contribute to the evolution of new genes
By jumping within an intron, they might have evolved into
alternatively spliced exons.
Jump would be followed by mutations that gave rise to splicing
recognition sites.
Alu sequences have given rise to
primate specific exons

More than 6% of human exons contain Alu sequeces

Most, if not all the Alu containing exons in humans are
alternatively spliced.